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Article: Molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, China

TitleMolecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, China
Authors
KeywordsFluoroquinolone Resistance
Gyrase Mutations
Mycobacterium Tuberculosis
Issue Date2012
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/diagmicrobio
Citation
Diagnostic Microbiology and Infectious Disease, 2012, v. 73 n. 3, p. 260-263 How to Cite?
AbstractChina is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQ r) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQ r M. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQ r M. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQ r M. tuberculosis strains and 21 ofloxacin-sensitive (FQ s) M. tuberculosis strains were isolated from patients with pulmonary tuberculosis in Shanghai. The phenotypic drug susceptibilities were determined by the proportion method, and the mutations inside quinolone resistance-determining region (QRDR) of gyrA and gyrB genes were identified by DNA sequence analyses. Among 206 FQ r M. tuberculosis strains, 44% (90/206) were multidrug-resistant isolates and 39% (81/206) were extensively drug-resistant isolates. Only 9% (19/206) were monoresistant to ofloxacin. In total, 79.1% (163/206) of FQ r isolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7% (156/206) of FQ r clinical isolates. Among those gyrA mutants, a majority (75.6%) harboured mutations at amino acid position 94, with D94G being the most frequent amino acid substitution. Mutations in gyrA QRDR showed 100% positive predictive value for FQ r M. tuberculosis in China. Mutations in gyrB were observed in 15.5% (32/206) of FQ r clinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQ r resistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQ r resistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQ r M. tuberculosis in China. © 2012 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/157707
ISSN
2015 Impact Factor: 2.45
2015 SCImago Journal Rankings: 1.142
ISI Accession Number ID
Funding AgencyGrant Number
National Science and Technology Council2008ZX10001-008
2009ZX10003-017
Funding Information:

This study was supported by two grants from the major programs of the National Science and Technology Council during the Eleventh Five-Year Plan Period (nos. 2008ZX10001-008 and 2009ZX10003-017).

References

 

DC FieldValueLanguage
dc.contributor.authorZhu, Cen_US
dc.contributor.authorZhang, Yen_US
dc.contributor.authorShen, Yen_US
dc.contributor.authorSiu, GKHen_US
dc.contributor.authorWu, Wen_US
dc.contributor.authorQian, Xen_US
dc.contributor.authorDeng, Gen_US
dc.contributor.authorXu, Yen_US
dc.contributor.authorLau, Ren_US
dc.contributor.authorFan, Xen_US
dc.contributor.authorZhang, Wen_US
dc.contributor.authorLu, Hen_US
dc.contributor.authorYam, WCen_US
dc.date.accessioned2012-08-08T08:52:27Z-
dc.date.available2012-08-08T08:52:27Z-
dc.date.issued2012en_US
dc.identifier.citationDiagnostic Microbiology and Infectious Disease, 2012, v. 73 n. 3, p. 260-263en_US
dc.identifier.issn0732-8893en_US
dc.identifier.urihttp://hdl.handle.net/10722/157707-
dc.description.abstractChina is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQ r) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQ r M. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQ r M. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQ r M. tuberculosis strains and 21 ofloxacin-sensitive (FQ s) M. tuberculosis strains were isolated from patients with pulmonary tuberculosis in Shanghai. The phenotypic drug susceptibilities were determined by the proportion method, and the mutations inside quinolone resistance-determining region (QRDR) of gyrA and gyrB genes were identified by DNA sequence analyses. Among 206 FQ r M. tuberculosis strains, 44% (90/206) were multidrug-resistant isolates and 39% (81/206) were extensively drug-resistant isolates. Only 9% (19/206) were monoresistant to ofloxacin. In total, 79.1% (163/206) of FQ r isolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7% (156/206) of FQ r clinical isolates. Among those gyrA mutants, a majority (75.6%) harboured mutations at amino acid position 94, with D94G being the most frequent amino acid substitution. Mutations in gyrA QRDR showed 100% positive predictive value for FQ r M. tuberculosis in China. Mutations in gyrB were observed in 15.5% (32/206) of FQ r clinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQ r resistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQ r resistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQ r M. tuberculosis in China. © 2012 Elsevier Inc.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/diagmicrobioen_US
dc.relation.ispartofDiagnostic Microbiology and Infectious Diseaseen_US
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Diagnostic Microbiology and Infectious Disease. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Diagnostic Microbiology and Infectious Disease, 2012, v. 73 n. 3, p. 260-263. DOI: 10.1016/j.diagmicrobio.2012.03.025-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectFluoroquinolone Resistanceen_US
dc.subjectGyrase Mutationsen_US
dc.subjectMycobacterium Tuberculosisen_US
dc.titleMolecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, Chinaen_US
dc.typeArticleen_US
dc.identifier.emailYam, WC:wcyam@hkucc.hku.hken_US
dc.identifier.authorityYam, WC=rp00313en_US
dc.description.naturepostprinten_US
dc.identifier.doi10.1016/j.diagmicrobio.2012.03.025en_US
dc.identifier.pmid22560167-
dc.identifier.scopuseid_2-s2.0-84862228470en_US
dc.identifier.hkuros225966-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84862228470&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume73en_US
dc.identifier.issue3en_US
dc.identifier.spage260en_US
dc.identifier.epage263en_US
dc.identifier.isiWOS:000305546300011-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhu, C=55207092400en_US
dc.identifier.scopusauthoridZhang, Y=8388259800en_US
dc.identifier.scopusauthoridShen, Y=16744841200en_US
dc.identifier.scopusauthoridSiu, GKH=35485473100en_US
dc.identifier.scopusauthoridWu, W=55092567600en_US
dc.identifier.scopusauthoridQian, X=55206172000en_US
dc.identifier.scopusauthoridDeng, G=55093419200en_US
dc.identifier.scopusauthoridXu, Y=55206462600en_US
dc.identifier.scopusauthoridLau, R=36664762000en_US
dc.identifier.scopusauthoridFan, X=11339198400en_US
dc.identifier.scopusauthoridZhang, W=55116934700en_US
dc.identifier.scopusauthoridLu, H=7404842614en_US
dc.identifier.scopusauthoridYam, WC=7004281720en_US
dc.identifier.citeulike10642216-

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